Long-term assessment of esophageal remodeling in patients with pediatric eosinophilic esophagitis treated with topical corticosteroids

Jessica Rajan; Robert O Newbury; Arjun Anilkumar; Ranjan Dohil; David H Broide; Seema S Aceves

doi:10.1016/j.jaci.2015.05.045

Long-term assessment of esophageal remodeling in patients with pediatric eosinophilic esophagitis treated with topical corticosteroids

J Allergy Clin Immunol. 2016 Jan;137(1):147-156.e8. doi: 10.1016/j.jaci.2015.05.045. Epub 2015 Jul 30.

Authors

Jessica Rajan¹, Robert O Newbury², Arjun Anilkumar³, Ranjan Dohil⁴, David H Broide⁵, Seema S Aceves⁶

Affiliations

¹ Division of Allergy and Immunology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Center for Immunity, Infection, and Inflammation, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Pediatrics, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif.
² Division of Pathology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Pediatrics, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif.
³ Division of Allergy and Immunology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Center for Immunity, Infection, and Inflammation, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Pediatrics, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Medicine, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif.
⁴ Division of Gastroenterology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Medicine, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif.
⁵ Division of Allergy and Immunology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Medicine, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif.
⁶ Division of Allergy and Immunology, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Center for Immunity, Infection, and Inflammation, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Pediatrics, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif; Department of Medicine, University of California, San Diego, La Jolla, Rady Children's Hospital San Diego, San Diego, Calif. Electronic address: saceves@ucsd.edu.

Abstract

Background: Eosinophilic esophagitis (EoE) is a chronic TH2 inflammatory disease characterized by tissue remodeling that leads to esophageal strictures and food impactions. Effects of therapy on long-term remodeling in patients with pediatric eosinophil-associated diseases have not been previously described.

Objective: We sought to understand the long-term control of esophageal remodeling in patients with EoE.

Methods: We assessed endoscopic and histologic remodeling and TGF-β1 expression in esophageal biopsy specimens from children (n = 32) with EoE treated with topical corticosteroids (TCSs) over 10 years (mean, 4.5 years). We used standardized EoE scoring tools to gauge endoscopic and symptom features.

Results: Seven hundred thirty-eight biopsy specimens from 246 endoscopic procedures were evaluated over 10 years. Four hundred eighty-six biopsy specimens had adequate lamina propria for evaluation of subepithelial remodeling. The severity of epithelial esophageal eosinophilia correlated with epithelial remodeling (basal zone hyperplasia, desquamation, and dilated intercellular spaces; P < .0001), lamina propria eosinophilia (P < .0001), and fibrosis (P < .0001). Sixteen subjects were initial responders (<15 eosinophils/high-power field) to TCSs. Responders and nonresponders spent 54% and 97% of their total disease duration with active EoE (P < .001) and 23% and 53% (P < .02) with maximal fibrosis scores, respectively. Responders had lower endoscopy scores during their disease duration (P = .013). Having less than 15 eosinophils/high-power field at any time correlated with lower fibrosis and endoscopic severity. TGF-β1(+) cell counts decreased in responders at the first biopsy, but this was not sustained. Symptoms did not correlate with other disease features.

Conclusions: Children with EoE have substantial esophageal remodeling, which associates with inflammation and can improve in a sustainable manner with TCSs. Although endoscopic features correspond to histologic features, symptoms did not correlate with inflammation or fibrosis.

Keywords: Eosinophilic esophagitis; TGF-β1; fibrosis; remodeling; topical corticosteroid.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Administration, Topical
Adolescent
Child
Child, Preschool
Eosinophilic Esophagitis / drug therapy*
Eosinophilic Esophagitis / metabolism
Eosinophilic Esophagitis / pathology*
Esophagus / metabolism
Esophagus / pathology*
Female
Glucocorticoids / administration & dosage
Glucocorticoids / therapeutic use*
Humans
Infant
Male
Proton Pump Inhibitors / therapeutic use
Transforming Growth Factor beta1 / metabolism

Substances

Glucocorticoids
Proton Pump Inhibitors
Transforming Growth Factor beta1

Abstract

Publication types

MeSH terms

Substances

Grants and funding